Conditions Affecting A1C and Fasting Blood Glucose Measurements

Conditions That Falsely Lower A1C

The American Diabetes Association recommends suspecting conditions that increase red blood cell turnover or alter hemoglobin structure when A1C and fasting glucose appear normal but diabetes may still be present, and relying exclusively on plasma glucose testing to diagnose diabetes in these situations 1.
Hemolytic anemias and blood loss can shorten the lifespan of red blood cells, reducing the time available for glucose to bind to hemoglobin, resulting in artificially low A1C readings despite elevated blood glucose, particularly in patients with recent blood loss or transfusion within the past 2-3 months 1, 2.
Hemoglobinopathies, such as sickle cell disease and glucose-6-phosphate dehydrogenase (G6PD) deficiency, can interfere with A1C measurement, resulting in falsely low readings 1, 2.
Pregnancy, particularly in the second and third trimesters and the postpartum period, can affect A1C reliability due to increased red blood cell turnover 1, 2.
Hemodialysis, chronic kidney disease requiring dialysis, and erythropoietin therapy can also impact A1C measurements, leading to falsely low readings 1, 2.

The American Diabetes Association recommends using plasma blood glucose criteria to diagnose diabetes, rather than relying on A1C alone, in conditions that affect A1C measurement, such as hemolytic anemias, hemoglobinopathies, and pregnancy 1, 2.
Fasting plasma glucose (FPG) ≥126 mg/dL, 2-hour plasma glucose during oral glucose tolerance test (OGTT) ≥200 mg/dL, and random plasma glucose ≥200 mg/dL can be used to diagnose diabetes in these situations 1, 3.

The American Diabetes Association recommends ensuring adequate carbohydrate intake of at least 150 g/day for 3 days prior to testing to avoid falsely low fasting glucose results from carbohydrate restriction 1, 3.
Glucose samples must be spun and separated immediately after collection to avoid falsely low glucose levels due to ongoing glycolysis by blood cells 4.

African American individuals may have A1C levels that are 0.3-0.8% higher than non-Hispanic White individuals with similar glucose levels, independent of hemoglobin variants, which can impact diagnosis and treatment 1, 3.

The American Diabetes Association recommends that diagnosis requires two abnormal test results from either the same sample or two separate samples in the absence of unequivocal hyperglycemia (symptoms plus random glucose ≥200 mg/dL) 1, 3.

For patients with hemoglobin variants but normal red blood cell turnover, the American Diabetes Association recommends using an A1C assay specifically validated to be free from interference with that particular hemoglobin variant 1, 2.